Techniques using targeted and controllable MR probes will be developed to extend the clinical application of iron oxide nanoparticle contrast agents. The project develops: theories and studies of coating characteristics to enhance the effect on the MR signal (Specific Aim 1), controllable and activatable contrast systems (Specific Aim 2), and alternative contrast mechanisms and imaging approaches for positive contrast (Specific Aim 3) to extend the use of MR imaging to acquire information on the molecular level. Such probes allow targeting and delineating areas of specific molecular activity on an MR image. Contrast agents activated under specific, controlled circumstances, such as the expression of a carcinogenic genotype, can be used to obtain images that provide molecular, as well as anatomical information. Applications focused on clinical diagnosis represent a non-invasive tool for health care reducing the need for surgical biopsy which carries health risks, such as morbidity and mortality. For organs where biopsy options are limited, such as the brain, this "virtual biopsy" represents a new tool for clinical management.